Collagen, elastin and proteoglycans are the principal structural elements of the connective tissues. The type and quantity of collagen present in a tissue seems to be responsible for its functional properties. Since environmental factors (nutrients, O2, hormones, lysosomal enzymes, etc.) affect cell function, we plan to investigate how they alter the cells ability to synthesize collagen, in particular how it affects the nature of the molecules synthesized (Type I, II, III, IV, AB, and X2Y). Our findings over the last year point to a major difference in chondrocyte metabolic activity, where cells are maintained in either cell or organ culture. Whereas in cell culture the chondrocytes lose their phenotypic specificity (ability to synthesize Type II collagen) after 4 passages, when they maintained in organ culture they retain it. We therefore feel that a "chondrogenic factor" may be responsible and we are pursuing this hypothesis. A fibroblast stimulating factor was detected in serum of pretibial myxedema patients, one which has a stimulatory activity on only fibroblasts originating from one area of the body, the pretibial area (not the back or arm). These findings also point towards specific mesenchymal cell modulators. Their characterization should be of great value in further understanding the abnormal behavior of such cells in many of the inflammatory and degenerative diseases of the connective tissues.